Secretion of enkephalin-like peptides from adrenal glands into circulation was studied in dogs with indwelling cannulae in adrenal vein. The stimulation of the splanchnic nerve induces a voltage dependent increase of met5-enkephalin immuno-reactive peptide (MEIP) in plasma. The MEIP secreted was identified to be met5-enkephalin using Bio-Gel P-2 column chromatography followed by high pressure liquid chromatography. The effect of splanchnic nerve stimulation was antagonized by hexamethonium suggesting that the release of MEIP was mediated through activation of nicotinic receptor. This suggestion was further supported by the fact that dimethlyphenylpiperazinium induced an increase of circulating MEIP. Morphine injection was found to induce a pronounced increase of plasma MEIP in intact dogs but not in splanchnic nerve transected dogs. This effect was blocked by naloxone and also by hexamethonium. The results suggest that the effect of morphine is centrally mediated. This study clearly indicates that enkephalin-like peptides in chromaffin cells of adrenal glands can be secreted into circulation.